Distinct frontal and amygdala correlates of change detection for facial identity and expression

Recruitment of ‘top-down’ frontal attentional mechanisms is held to support detection of changes in task-relevant stimuli. Fluctuations in intrinsic frontal activity have been shown to impact task performance more generally. Meanwhile, the amygdala has been implicated in ‘bottom-up’ attentional capture by threat. Here, 22 adult human participants took part in a functional magnetic resonance change detection study aimed at investigating the correlates of successful ( vs failed) detection of changes in facial identity vs expression. For identity changes, we expected prefrontal recruitment to differentiate ‘hit’ from ‘miss’ trials, in line with previous reports. Meanwhile, we postulated that a different mechanism would support detection of emotionally salient changes. Specifically, elevated amygdala activation was predicted to be associated with successful detection of threat-related changes in expression, over-riding the influence of fluctuations in top-down attention. Our findings revealed that fusiform activity tracked change detection across conditions. Ventrolateral prefrontal cortical activity was uniquely linked to detection of changes in identity not expression, and amygdala activity to detection of changes from neutral to fearful expressions. These results are consistent with distinct mechanisms supporting detection of changes in face identity vs expression, the former potentially reflecting top-down attention, the latter bottom-up attentional capture by stimulus emotional salience

Moderate threat causes longer lasting disruption to processing in anxious individuals

Anxiety is associated with increased attentional capture by threat. Previous studies have used simultaneous or briefly separated (<1 s) presentation of threat distractors and target stimuli. Here, we tested the hypothesis that high trait anxious participants would show a longer time window within which distractors cause disruption to subsequent task processing, and that this would particularly be observed for stimuli of moderate or ambiguous threat value. A novel temporally separated emotional distractor task was used. Face or house distractors were presented for 250 ms at short (∼1.6 s) or long (∼3 s) intervals prior to a letter string comprising Xs or Ns. Trait anxiety was associated with slowed identification of letter strings presented at long intervals after face distractors with part surprise/part fear expressions. In other words, these distractors had an impact on high anxious individuals' speed of target identification seconds after their offset. This was associated with increased activity in the fusiform gyrus and amygdala and reduced dorsal anterior cingulate recruitment. This pattern of activity may reflect impoverished recruitment of reactive control mechanisms to damp down stimulus-specific processing in subcortical and higher visual regions. These findings have implications for understanding how threat-related attentional biases in anxiety may lead to dysfunction in everyday settings where stimuli of moderate, potentially ambiguous, threat value such as those used here are fairly common, and where attentional disruption lasting several seconds may have a profound impact

Estimating The Costs And Cost-effectiveness Of Promoting Mammography Screening Among US-based Latinas

Purpose: We characterize the costs and cost-effectiveness of a community health worker (CHW)-based intervention to promote screening mammography among US-based non-adherent Latinas. Methods: The parent study was a randomized controlled trial for 536 Latinas aged 42-74 years old who had sought care within a safety net health center in Western Washington. Participants were block-randomized within clinic to the control arm (usual care) or intervention arm (CHW-led motivational interviewing intervention). We used the perspective of the organization implementing promotional activities to characterize costs and cost-effectiveness. Cost data were categorized as program set-up and maintenance (initial training, booster/annual training) program implementation (administrative activities, intervention delivery); and, overhead/miscellaneous expenses. Cost-effectiveness was calculated as the incremental cost of screening for each additional woman screened between the intervention and control arms. Results: The respective costs per participant for standard care and the intervention arm were $69.96 and$300.99. There were no study arm differences in 1-year QALYs among women who completed a 12-month follow-up survey (intervention= 0.8827, standard care = 0.8841). Most costs pertained to program implementation and administrative activities specifically. The incremental cost per additional woman screened was $2,595.32. Conclusions: Our findings are within the ranges of costs and cost-effectiveness for other CHW programs to promote screening mammography among underserved populations. Our strong study design and focus on non-adherent women provides important strengths to this body of work, especially give implementation and dissemination science efforts regarding CHW-based health promotion for health disparity populations

Seeing the world through non rose-colored glasses: anxiety and the amygdala response to blended expressions

Anxious individuals have a greater tendency to categorize faces with ambiguous emotional expressions as fearful (Richards et al., 2002). These behavioral findings might reflect anxiety-related biases in stimulus representation within the human amygdala. Here, we used functional magnetic resonance imaging (fMRI) together with a continuous adaptation design to investigate the representation of faces from three expression continua (surprise-fear, sadness-fear, and surprise-sadness) within the amygdala and other brain regions implicated in face processing. Fifty-four healthy adult participants completed a face expression categorization task. Nineteen of these participants also viewed the same expressions presented using type 1 index 1 sequences while fMRI data were acquired. Behavioral analyses revealed an anxiety-related categorization bias in the surprise-fear continuum alone. Here, elevated anxiety was associated with a more rapid transition from surprise to fear responses as a function of percentage fear in the face presented, leading to increased fear categorizations for faces with a mid-way blend of surprise and fear. fMRI analyses revealed that high trait anxious participants also showed greater representational similarity, as indexed by greater adaptation of the Blood Oxygenation Level Dependent (BOLD) signal, between 50/50 surprise/fear expression blends and faces from the fear end of the surprise-fear continuum in both the right amygdala and right fusiform face area (FFA). No equivalent biases were observed for the other expression continua. These findings suggest that anxiety-related biases in the processing of expressions intermediate between surprise and fear may be linked to differential representation of these stimuli in the amygdala and FFA. The absence of anxiety-related biases for the sad-fear continuum might reflect intermediate expressions from the surprise-fear continuum being most ambiguous in threat-relevance

Resting state correlates of subdimensions of anxious affect

Resting state fMRI may help identify markers of risk for affective disorder. Given the comorbidity of anxiety and depressive disorders and the heterogeneity of these disorders as defined by DSM, an important challenge is to identify alterations in resting state brain connectivity uniquely associated with distinct profiles of negative affect. The current study aimed to address this by identifying differences in brain connectivity specifically linked to cognitive and physiological profiles of anxiety, controlling for depressed affect. We adopted a two-stage multivariate approach. Hierarchical clustering was used to independently identify dimensions of negative affective style and resting state brain networks. Combining the clustering results, we examined individual differences in resting state connectivity uniquely associated with subdimensions of anxious affect, controlling for depressed affect. Physiological and cognitive subdimensions of anxious affect were identified. Physiological anxiety was associated with widespread alterations in insula connectivity, including decreased connectivity between insula subregions and between the insula and other medial frontal and subcortical networks. This is consistent with the insula facilitating communication between medial frontal and subcortical regions to enable control of physiological affective states. Meanwhile, increased connectivity within a frontoparietal-posterior cingulate cortex-precunous network was specifically associated with cognitive anxiety, potentially reflecting increased spontaneous negative cognition (e.g., worry). These findings suggest that physiological and cognitive anxiety comprise subdimensions of anxiety-related affect and reveal associated alterations in brain connectivity

Distinct frontal and amygdala correlates of change detection for facial identity and expression

Abstract Recruitment of &apos;top-down&apos; frontal attentional mechanisms is held to support detection of changes in task-relevant stimuli. Fluctuations in intrinsic frontal activity have been shown to impact task performance more generally. Meanwhile, the amygdala has been implicated in &apos;bottom-up&apos; attentional capture by threat. Here, 22 adult human participants took part in a functional magnetic resonance change detection study aimed at investigating the correlates of successful (vs failed) detection of changes in facial identity vs expression. For identity changes, we expected prefrontal recruitment to differentiate &apos;hit&apos; from &apos;miss&apos; trials, in line with previous reports. Meanwhile, we postulated that a different mechanism would support detection of emotionally salient changes. Specifically, elevated amygdala activation was predicted to be associated with successful detection of threat-related changes in expression, over-riding the influence of fluctuations in top-down attention. Our findings revealed that fusiform activity tracked change detection across conditions. Ventrolateral prefrontal cortical activity was uniquely linked to detection of changes in identity not expression, and amygdala activity to detection of changes from neutral to fearful expressions. These results are consistent with distinct mechanisms supporting detection of changes in face identity vs expression, the former potentially reflecting top-down attention, the latter bottom-up attentional capture by stimulus emotional salience

Impaired adaptation of learning to contingency volatility in internalizing psychopathology

Using a contingency volatility manipulation, we tested the hypothesis that difficulty adapting probabilistic decision-making to second-order uncertainty might reflect a core deficit that cuts across anxiety and depression and holds regardless of whether outcomes are aversive or involve reward gain or loss. We used bifactor modeling of internalizing symptoms to separate symptom variance common to both anxiety and depression from that unique to each. Across two experiments, we modeled performance on a probabilistic decision-making under volatility task using a hierarchical Bayesian framework. Elevated scores on the common internalizing factor, with high loadings across anxiety and depression items, were linked to impoverished adjustment of learning to volatility regardless of whether outcomes involved reward gain, electrical stimulation, or reward loss. In particular, high common factor scores were linked to dampened learning following better-than-expected outcomes in volatile environments. No such relationships were observed for anxiety- or depression-specific symptom factors

Stratification of MDD and GAD patients by resting state brain connectivity predicts cognitive bias

Patients with Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) show between-group comorbidity and symptom overlap, and within-group heterogeneity. Resting state functional connectivity might provide an alternate, biologically informed means by which to stratify patients with GAD or MDD. Resting state functional magnetic resonance imaging data were acquired from 23 adults with GAD, 21 adults with MDD, and 27 healthy adult control participants. We investigated whether within- or between-network connectivity indices from five resting state networks predicted scores on continuous measures of depression and anxiety. Successful predictors were used to stratify participants into two new groups. We examined whether this stratification predicted attentional bias towards threat and whether this varied between patients and controls. Depression scores were linked to elevated connectivity within a limbic network including the amygdala, hippocampus, VMPFC and subgenual ACC. Patients with GAD or MDD with high limbic connectivity showed poorer performance on an attention-to-threat task than patients with low limbic connectivity. No parallel effect was observed for control participants, resulting in an interaction of clinical status by resting state group. Our findings provide initial evidence for the external validity of stratification of MDD and GAD patients by functional connectivity markers. This stratification cuts across diagnostic boundaries and might valuably inform future intervention studies. Our findings also highlight that biomarkers of interest can have different cognitive correlates in individuals with versus without clinically significant symptomatology. This might reflect protective influences leading to resilience in some individuals but not others

Can Community Gardens with Workshops Increase Gardening Behavior? A Navajo Wellness Collaboration

This paper seeks to evaluate the potential efficacy of a community gardening intervention on the Navajo Nation to increase gardening and healthy eating behaviors, which are potentially important in preventing obesity and related health conditions. Rates of obesity are high among American Indians, including those living on Navajo Nation land. Eating fresh fruits and vegetables is part of healthy eating. However, availability and access to fresh fruits and vegetables are severely limited on the Navajo Nation, due to distance and cost. One way to increase both availability and consumption of fresh fruits and vegetables is through community gardening, yet many on the Navajo Nation have limited knowledge and capacity to garden. Methods: We used a quasi-experimental pre-post study design to estimate the effect of a community gardening intervention. Primary outcomes of interest were gardening frequency and fruit and vegetable consumption. Community gardens were constructed and planted in two communities on the Navajo Nation. In addition, a series of gardening workshops were held in each community. Community members were recruited to complete surveys at time points before and after the workshops. The time between baseline and follow-up was approximately one year. Results: We surveyed 169 participants at one time point at least, across both communities, and 25 of these participated in the gardening workshops. Within the 169, there was a cohort of 32 participants completing both baseline and follow-up surveys. For this cohort, interest in gardening increased from 78% to 97% (p=0.014), but none of the changes in gardening self-efficacy, knowledge or gardening frequency reached statistical significance. There were no measurable changes in reported fruit and vegetable consumption, self-efficacy or knowledge. Overall, the reported financial barriers to gardening increased from baseline to follow-up from 4.6 to 5.5 (p=0.035). Altogether 52 participants completed follow-up. In this group, those who attended at least one workshop gardened more frequently at follow-up than those who did not attend any workshops (21 times per month compared to 10 times per month (p=0.07). Conclusion: Despite enthusiasm for the community garden in both the communities studied and the increased interest in gardening, workshop attendance and participant retention in the study were low. These factors limited our ability to evaluate the potential efficacy of the intervention on gardening and healthy eating behaviors. Nonetheless, we found some evidence that participating in gardening workshops may lead to increased gardening frequency. Future studies should augment the intervention to include explicit efforts to reduce barriers to long term engagement and extend intervention reach

Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high‐risk acute myeloid leukaemia ineligible for intensive chemotherapy

Azacitidine (AZA) is important in the management of patients with acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. Romidepsin (ROM) is a histone deacetylase inhibitor which synergises with AZA in vitro. The ROMAZA trial established the maximum tolerated dose (MTD) of combined ROM/AZA therapy in patients with AML, as ROM 12 mg/m2 on Days 8 and 15, with AZA 75 mg/m2 administered for 7/28 day cycle. Nine of the 38 (23·7%) patients treated at the MTD were classified as responders by Cycle 6 (best response: complete remission [CR]/incomplete CR n = 7, partial response n = 2). Correlative next‐generation sequencing studies demonstrated important insights into therapy resistance